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Background: Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs.Methods and Results: We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11  887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; P=0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed.Conclusions: Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings. [ABSTRACT FROM AUTHOR]